O2 to be a friend or foe?

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Sabrina Kroft
Registered Respiratory Therapist for 18 years working in all areas of healthcare. Professional interest is the nuances of mechanical ventilation and just learning new/old technology.

The Pre-brief

Hyperoxia occurs when there is an excess supply of O2 available to the tissues and organs. Although normobaric hyperoxia can increase arterial oxygen content, it is also known to cause vasoconstriction, which reduces O2 delivery in various vascular beds including the heart, skeletal muscle, and brain. Oxygen is toxic to the lungs when high FiO2 (>0.60) is administered over extended exposure time. Oxygen exposure after approximately 12 hours leads to lung passageway congestion, pulmonary edema, and atelectasis caused by damage to the linings of the bronchi and alveoli. 


Clinicians should titrate O2 therapy to avoid both hypoxemia and hyperoxia. While the harmful effects of tissue hypoxia are clearly understood, over-correction leads to tissue hyperoxia, which may also be hazardous. Hyperoxia injuries cause oxidant stress with pro-inflammatory and cytotoxic effects. It appears prudent to target PaO2 values within an acceptable range, particularly as no clinically useful biomarker of O2 toxicity is available, and data on the effects of hyperoxia on markers of oxidative stress are equivocal.

While “optimal” dosing of oxygen remains unclear, it is known that you can have too much of a good thing.  The Oxygen-ICU trial was the first major study to suggest clinically important harm from liberal O2 administration in a general ICU population. This single-center, RCT included 480 patients expected to stay in the ICU for at least 72 hrs. The ICU mortality was 20.2% with conventional and 11.6% with conservative O2 therapy. Conversely, the LUNGSAFE study found no relationship between hyperoxia or excessive oxygen use and patient outcome. These conflicting results show the lack of informational studies on high concentrations of FiO2 use and hyperoxia. While severe degrees of systemic hypoxia associated with harm in other critically ill populations are not possible in ARDS, it is unclear that high concentrations of FiO2 exacerbate the disease process. 

Oxygen is not a harmless drug and its use should be treated as though it can have adverse side effects. Conservative oxygenation strategy target SpO2 of 90–92% should be utilized, as it was associated with lower incidence of new organ dysfunction. It seems clear that FiO2 should not be fixed, but rather titrated to achieve PaO2 or SpO2 targets. There is no reason to keep FiO2 high when SpO2 is 100% or at a satisfactory level for the patient.  Weaning oxygen should be immediately considered once a reasonable PaO2 level is achieved. Targeted PaO2 by disease process has not been largely studied, but the need is there. Respiratory Therapists should always be aware of the perils of hyperoxia and adjust therapy accordingly. 

The Debrief

  • Hyperoxia is excess O2 available to tissue and organs
  • High FiO2 concentrations should be monitored and weaned to achieve an acceptable PaO2
  • Oxygen is a drug that does cause adverse effects


  1. Highs and lows of hyperoxia: physiological, performance, and clinical aspects. Brugniaux, Julien Vincent, Coombs, Geoff B., Barak, Otto F., Dujic, Zeljko, Sekhon, Mypinder S., Ainslie, Philip N. (2018) https://doi.org/10.1152/ajpregu.00165.2017
  2. Hafner, S., Beloncle, F., Koch, A. et al. Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update. Ann. Intensive Care 5, 42 (2015). https://doi.org/10.1186/s13613-015-0084-6
  3. Girardis M, Busani S, Damiani E, Donati A, Rinaldi L, Marudi A, Morelli A, Antonelli M, Singer M. Effect of conservative vs conventional oxygen therapy on mortality among patients in an intensive care unit: the Oxygen-ICU randomized clinical trial. JAMA. 2016;316(15):1583–9.
  4. Mikkelsen ME, Anderson B, Christie JD, Hopkins RO, Lanken PN. Can we optimize long-term outcomes in acute respiratory distress syndrome by targeting normoxemia? Ann Am Thorac Soc 2014;11:613–618.
  5. Madotto, F., Rezoagli, E., Pham, T. et al. Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome: insights from the LUNG SAFE study. Crit Care 24, 125 (2020). https://doi.org/10.1186/s13054-020-2826-6


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